Intracranial tumors may involve the brain or other structures (eg, cranial nerves, meninges). The tumors usually develop during early or middle adulthood but may develop at any age; they are becoming more common among older people. Brain tumors are found in about 2% of routine autopsies.
Some tumors are benign, but because the cranial vault allows no room for expansion, even benign tumors can cause serious neurologic dysfunction or death.
Classification
There are 2 types of brain tumors:
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Primary brain tumors: Originate in the brain either in the brain parenchyma (eg, gliomas, which include astrocytomas, oligodendrogliomas, and ependymomas; medulloblastomas) or in extraneural structures (eg, meningiomas, acoustic neuromas, other schwannomas)
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Secondary brain tumors (brain metastases): Originate in tissues outside the brain and spread to the brain
Brain metastases are about 10 times more common than primary tumors.
Type of tumor varies somewhat by site (see table Common Localizing Manifestations of Primary Brain Tumors) and patient age (see table Common Tumors by Age).
Common Localizing Manifestations of Primary Brain Tumors
Tumor Site |
Findings |
Common Primary Tumor Types* |
|
Anterior corpus callosum |
Cognitive impairment |
Astrocytoma (including low-grade gliomas) |
|
Basal ganglia |
Hemiparesis (contralateral), movement disorders |
Astrocytoma (including low-grade gliomas) |
|
Brain stem |
Unilateral or bilateral motor or sensory loss, cranial nerve deficits (eg, gaze palsies, hearing loss, vertigo, palatal paresis, facial weakness), ataxia, intention tremor, nystagmus |
Astrocytoma (including juvenile pilocytic astrocytoma) Diffuse pontine glioma |
|
Cerebellopontine angle |
Tinnitus and hearing loss (both ipsilateral), vertigo, loss of vestibular response to caloric stimulation If tumor is large, ataxia, loss of facial sensation and facial weakness (both ipsilateral), possibly other cranial nerve or brain stem deficits |
Schwannoma |
|
Cerebellum |
Ataxia, nystagmus, tremor, hydrocephalus with suddenly increased intracranial pressure |
Astrocytoma (including juvenile pilocytic astrocytoma) |
|
2nd cranial (optic) nerve |
Loss of vision |
Astrocytoma (including pilocytic astrocytomas and lower-grade gliomas; optic nerve location most common in neurofibromatosis) |
|
5th cranial (trigeminal) nerve |
Loss of facial sensation, jaw weakness |
Meningioma Schwannoma |
|
Frontal lobe |
Generalized or focal (contralateral) seizures, gait disorders, urinary urgency or incontinence, impaired attention and cognition and apathy (particularly if tumor is bilateral), hemiparesis Expressive aphasia if tumor is in dominant hemisphere Anosmia if tumor is at base of lobe |
Astrocytoma Glioblastoma Oligodendroglioma |
|
Hypothalamus |
Eating and drinking disorders (eg, polydipsia), precocious puberty (especially in boys), hypothermia |
Astrocytoma |
|
Occipital lobe |
Generalized seizures with visual aura, visual hallucinations, hemianopia or quadrantanopia (contralateral) |
Astrocytoma Glioblastoma Oligodendroglioma |
|
Parietal lobe |
Deficits in position sensation and in 2-point discrimination (contralateral), anosognosia (no recognition of bodily defects), denial of illness, hemianopia (contralateral), generalized or focal seizures, inability to perceive (extinguishing of) a contralateral stimulus when stimuli are applied to both sides of the body (called double simultaneous stimulation) Receptive aphasia if tumor is in dominant hemisphere |
Astrocytoma Glioblastoma Oligodendroglioma |
|
Paresis of upward gaze, ptosis, loss of pupillary light and accommodation reflexes, sometimes hydrocephalus with suddenly increased intracranial pressure |
Germ cell tumor Pineocytoma (rare) |
|
|
Pituitary or suprasellar region |
Endocrinopathies, monocular visual loss, headache without increased intracranial pressure, bitemporal hemianopia |
Craniopharyngioma Pituitary carcinoma (rare) |
|
Temporal lobe |
Complex partial seizures, generalized seizures with or without aura, hemianopia (contralateral), mixed expressive and receptive aphasia or anomia |
Astrocytoma Glioblastoma Oligodendroglioma |
|
Thalamus |
Sensory impairment (contralateral) |
Astrocytoma |
|
* Similar manifestations may result from brain parenchymal metastases or from tumors around the dura (eg, metastatic tumors; meningeal tumors such as meningiomas, sarcomas, or gliomas) or skull lesions (eg, granulomas, hemangiomas, osteitis deformans, osteomas, xanthomas) that compress the underlying brain. |
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Common Brain Tumors by Age
Age Group |
Primary |
Metastases |
|
Children |
Cerebellar astrocytomas, juvenile pilocytic astrocytomas, and medulloblastomas Primitive neuroectodermal tumors and neurocytoma Gliomas of the brain stem or optic nerve Germinomas Congenital tumors* |
Neuroblastoma (usually epidural) Leukemia (meningeal) |
|
Adults |
Schwannomas Gliomas of the cerebral hemispheres, particularly glioblastoma, anaplastic astrocytoma, low-grade astrocytoma, pilocytic astrocytoma, and oligodendroglioma |
Bronchogenic carcinoma Adenocarcinoma of the breast, thyroid, or kidneys Malignant melanoma Metastatic lymphoma Any cancer that has spread to the lungs |
|
* Congenital tumors include craniopharyngiomas, chordomas, germinomas, teratomas, dermoid cysts, angiomas, and hemangioblastomas. |
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Pathophysiology
Neurologic dysfunction may result from the following:
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Invasion and destruction of brain tissue by the tumor
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Direct compression of adjacent tissue by the tumor
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Increased intracranial pressure (because the tumor occupies space within the skull)
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Bleeding within or outside the tumor
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Cerebral edema
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Obstruction of dural venous sinuses (especially by bone or extradural metastatic tumors)
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Obstruction of cerebrospinal fluid (CSF) drainage (occurring early with 3rd-ventricle or posterior fossa tumors)
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Obstruction of CSF absorption (eg, when leukemia or carcinoma involves the meninges)
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Obstruction of arterial flow
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Rarely, paraneoplastic syndromes
A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke. Bleeding as a complication of metastatic tumors is most likely to occur in patients with melanoma, renal cell carcinoma, choriocarcinoma, or thyroid, lung, or breast cancer.
Benign tumors grow slowly. They may become quite large before causing symptoms, partly because often there is no cerebral edema. Malignant primary tumors grow rapidly but rarely spread beyond the central nervous system (CNS). Death results from local tumor growth and thus can result from benign as well as malignant tumors. Therefore, distinguishing between benign and malignant is prognostically less important for brain tumors than for other tumors.
Symptoms and Signs
Symptoms caused by primary tumors and metastatic tumors are the same. Many symptoms result from increased intracranial pressure:
Headache is the most common symptom. Headache may be most intense when patients awake from deep nonrapid eye movement (non-REM) sleep (usually several hours after falling asleep) because hypoventilation, which increases cerebral blood flow and thus intracranial pressure, is usually maximal during non-REM sleep. Headache is also progressive and may be worsened by recumbency or the Valsalva maneuver. When intracranial pressure is very high, the headache may be accompanied by vomiting, sometimes with little nausea preceding it.
Papilledema develops in about 25% of patients with a brain tumor but may be absent even when intracranial pressure is increased. In infants and very young children, increased intracranial pressure may enlarge the head. If intracranial pressure increases sufficiently, brain herniation occurs.
Deterioration in mental status is the 2nd most common symptom. Manifestations include drowsiness, lethargy, personality changes, disordered conduct, and impaired cognition, particularly with malignant brain tumors. Airway reflexes may be impaired.
Focal brain dysfunction causes some symptoms. Focal neurologic deficits, endocrine dysfunction, or focal seizures (sometimes with secondary generalization) may develop depending on the tumor’s location (see table Common Localizing Manifestations of Brain Tumors). Focal deficits often suggest the tumor’s location. However, sometimes focal deficits do not correspond to the tumor’s location. Such deficits, called false localizing signs, include the following:
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Unilateral or bilateral lateral rectus palsy (with paresis of eye abduction) due to increased intracranial pressure compressing the 6th cranial nerve
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Ipsilateral hemiplegia due to compression of the contralateral cerebral peduncle against the tentorium (Kernohan notch)
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Ipsilateral visual field defect due to ischemia in the contralateral occipital lobe
Generalized seizures may occur, more often with primary than metastatic brain tumors. Impaired consciousness can result from herniation, brain stem dysfunction, or diffuse bilateral cortical dysfunction.
Some tumors cause meningeal inflammation, resulting in subacute or chronic meningitis.
Diagnosis
Early-stage brain tumors are often misdiagnosed. A brain tumor should be considered in patients with any of the following:
Similar findings can result from other intracranial masses (eg, abscess, aneurysm, arteriovenous malformation, intracerebral hemorrhage, subdural hematoma, granuloma, parasitic cysts such as neurocysticercosis) or ischemic stroke.
A complete neurologic examination, neuroimaging, and chest x-rays (for a source of metastases) should be done. T1-weighted MRI with gadolinium is the study of choice. CT with contrast agent is an alternative. MRI usually detects low-grade astrocytomas and oligodendrogliomas earlier than CT and shows brain structures near bone (eg, the posterior fossa) more clearly. If whole-brain imaging does not show sufficient detail in the target area (eg, sella turcica, cerebellopontine angle, optic nerve), closely spaced images or other special views of the area are obtained. If neuroimaging is normal but increased intracranial pressure is suspected, idiopathic intracranial hypertension should be considered and lumbar puncture done.
Radiographic clues to the type of tumor, mainly location (see table Common Localizing Manifestations of Brain Tumors) and pattern of enhancement on MRI, may be inconclusive; brain biopsy, sometimes excisional biopsy, may be required.
Specialized tests (eg, molecular and genetic tumor markers in blood and CSF) can help in some cases. In patients with AIDS, Epstein-Barr virus titers in CSF typically increase as CNS lymphoma develops.
Treatment
Patients in a coma or with impaired airway reflexes require endotracheal intubation.
Brain herniation due to tumors is treated with mannitol 25 to 100 g infused IV, a corticosteroid (eg, dexamethasone 16 mg IV, followed by 4 mg orally or IV every 6 hours), and endotracheal intubation. Hyperventilation to a carbon dioxide partial pressure (PCO2) of 26 to 30 mm Hg can help decrease intracranial pressure temporarily in emergencies. Mass lesions should be surgically decompressed as soon as possible.
Increased intracranial pressure due to tumors but without herniation can be treated with corticosteroids (eg, dexamethasone 4 mg orally every 6 to12 hours or prednisone 30 to 40 mg orally twice a day).
Treatment of the brain tumor depends on pathology and location (for acoustic neuroma, see Acoustic Neuroma). Surgical excision should be used for diagnosis (excisional biopsy) and symptom relief. It may cure benign tumors. For tumors infiltrating the brain parenchyma, treatment is multimodal. Radiation therapy is required, and chemotherapy appears to benefit some patients.
Treatment of metastatic tumors includes radiation therapy and sometimes stereotactic radiosurgery. For patients with a single metastasis, surgical excision of the tumor before radiation therapy improves outcome.
End-of-life issues
If patients have an incurable tumor, end-of-life issues should be discussed, and palliative care consultation should be considered.
Cranial Radiation Therapy and Neurotoxicity
Radiation therapy may be directed diffusely to the whole head for diffuse or multicentric tumors or locally for well-demarcated tumors.
Localized brain radiation therapy may be conformal, targeting the tumor with the aim of sparing normal brain tissue, or stereotactic, typically involving gamma knife or proton beam therapy. Gliomas are treated with conformal radiation therapy; a stereotactically directed gamma knife or proton beam therapy is useful for metastases. Current recommendations are to treat ≤ 4 metastatic lesions with stereotactic or other focal radiation interventions and to treat> 4 lesions with whole-brain radiation therapy (1). Giving radiation in smaller fractionated daily doses tends to maximize efficacy while minimizing neurotoxicity and damage to normal CNS tissue (see Radiation Exposure and Contamination).
Degree of neurotoxicity depends on
Because susceptibility varies, prediction of radiation neurotoxicity is imprecise. Symptoms can develop in the first few days (acute) or months of treatment (early-delayed) or several months to years after treatment (late-delayed). Rarely, radiation causes gliomas, meningiomas, or peripheral nerve sheath tumors years after therapy.
Acute radiation neurotoxicity
Typically, acute neurotoxicity involves headache, nausea, vomiting, somnolence, and sometimes worsening focal neurologic signs in children and adults.
Acute neurotoxicity largely results from transient swelling and edema; thus, it is particularly likely if intracranial pressure is already high. Using corticosteroids to lower intracranial pressure can prevent or treat acute toxicity. Acute toxicity lessens with subsequent treatments.
Early-delayed neurotoxicity
In children or adults, early-delayed neurotoxicity can cause encephalopathy, which must be distinguished by MRI or CT from worsening or recurrent brain tumor. It may occur in children who have received prophylactic whole-brain radiation therapy for leukemia; they may develop somnolence, which lessens spontaneously over several days to weeks, possibly more rapidly if corticosteroids are used.
After radiation therapy to the neck or upper thorax, early-delayed neurotoxicity can result in a myelopathy, characterized by spinal symptoms such as Lhermitte sign (an electric shock-like sensation radiating down the back and into the legs when the neck is flexed). This early-delayed myelopathy typically resolves spontaneously.
Late-delayed neurotoxicity
After diffuse or whole-brain radiation therapy, many children and adults develop late-delayed neurotoxicity if they survive long enough. The most common cause in children is diffuse therapy given to prevent leukemia or to treat medulloblastoma. After diffuse therapy, the most common symptom is progressive dementia; adults may also develop an unsteady gait and focal neurologic symptoms. MRI or CT can show cerebral atrophy and often white matter loss.
After localized therapy, neurotoxicity more often involves focal neurologic deficits.
MRI or CT shows a mass that may be enhanced by contrast agent and that may be difficult to distinguish from recurrence of the primary tumor. Excisional biopsy of the mass is diagnostic and often ameliorates symptoms.
Late-delayed myelopathy can develop after radiation therapy for extraspinal tumors (eg, due to Hodgkin lymphoma). It is characterized by progressive paresis and sensory loss, often as a Brown-Séquard syndrome (ipsilateral paresis and proprioceptive sensory loss, with contralateral loss of pain and temperature sensation). Most patients eventually become paraplegic.
Treatment reference
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1. Gaspar L, Prabhu R, Hdeib A, et al: Congress of Neurological Surgeons systematic review and evidence-based guidelines on the role of whole brain radiation therapy in adults with newly diagnosed metastatic brain tumors. Neurosurgery 84 (3):E159–E162, 2019. doi: 10.1093/neuros/nyy541
